A hydrogel is useful as a gel having high biocompatibility because it includes water as a medium, and thus is used in wide fields including commodities such as disposable diapers, cosmetics, and air fresheners.
Examples of a conventional hydrogel include natural polymer gels such as agarose and synthetic polymer gels that are formed by cross-linking chains of a polymer such as an acrylamide gel through chemical covalent bonds.
Recently, functional gels in which various functions such as substance holding capacities, external stimulus responsive performance, and biodegradability in consideration of the environment are imparted to a hydrogel have been attracting much attention, and there are attempts for providing various functions by incorporating functional molecules into the natural or the synthetic polymer gels using copolymerization reaction.
In order to impart a new function to a hydrogel, it is required to study the nanostructure and the surface structure of the gel in detail. However, the method of incorporating a functional molecule using the copolymerization reaction has various problems that the introduction rate of a functional group is limited, that precise molecular design is difficult, that unreacted residual substances have safety issues, and that gel preparation is extremely complicated.
In order to prepare a safe and stable sheet-shaped gel (so-called a gel sheet) without unreacted residual crosslinking agents using such hydrogels, a solution dissolving a natural polymer is placed in a sheet-shape mold and a gel sheet is formed by gelation. However, physical cross-linkages between natural polymers are fragile and in an equilibrium state. Thus, when the gel sheet is immersed in water, the natural polymer is gradually fallen out from the gel sheet into water to disintegrate the gel sheet. In this manner, it has been extremely difficult to prepare a gel sheet only by a physical gel (Non-patent Document 1).
In contrast to such conventional “top-down type” developments of functional materials, “bottom-up type” studies for producing functional materials, in which atoms or molecules as a minimum unit of substances are assembled to form an assembly and a new function is found in a supermolecule as the formed assembly, have been drawing attention.
Also in the field of gels, a new gel composed of a noncovalent gel fiber (so-called “nanofiber self-assembly”) has been developed by self-assembly of low molecular compounds. The “self-assembly” means that, in a substance (molecule) group in a random state at first, molecules are spontaneously assembled under suitable external conditions through intermolecular noncovalent interactions and the like to grow to a macro functional assembly.
The new gel draws attention because macroscopic structures or functions of the gel can be theoretically controlled by controlling intermolecular interactions or weak noncovalent bonds of a molecular assembly depending on molecular design of monomers.
However, there is no definite method for controlling the intermolecular interactions or the noncovalent bonds between low-molecular weight compounds. Furthermore, in the studies of the noncovalent gel, the study of self-assembly using hydrogen bonds in an organic solvent is preceded because the gel is comparatively easily formed, and self-assembled compounds in an aqueous solution (that is, a hydrogelator and the like) have been found only incidentally.
Previously reported hydrogelators forming noncovalent gels are generally classified into the following three types.
[1. Hydrogelators Having Amphiphilic Low-Molecular Weight Molecule as Skeleton]
This type of hydrogelators is modeled on an artificial lipid membrane. Examples of the hydrogelator include surfactant gelators having a quaternary ammonium salt part as the hydrophilic portion and an alkyl long chain as the hydrophobic portion and twin-surfactant gelators in which hydrophilic portions of two surfactant molecules are connected.
As an example of the hydrogel produced by such gelators, there has been developed a molecular organizational hydrogel formed by adding an anionic compound having a molecular weight of 90 or more to an aqueous solution dispersing a cationic amphiphilic compound having a branched alkyl group as the hydrophobic portion (Patent Document 1).
[2. Hydrogelators Having Skeleton in Motif of Biocomponents]
Examples of the hydrogelator include gelators using assembly between molecular assemblies by a peptide secondary structure skeleton (such as an α-helix structure and a β-sheet structure).
For example, there has been developed a gelator having an α-helix structure (Non-patent Document 2) and a gelator having a β-sheet structure (Non-patent Document 3).
[3. Hydrogelators Having Semi-Artificial Low-Molecular Weight Molecule as Skeleton]
This type of hydrogelators is composed of a combination of a biocomponent such as DNA bases, peptide chains, and sugar chains (hydrophilic portion), an alkyl chain (hydrophobic portion), and the like, and can be considered as a gelator in which the characteristics of the above two types of gelators are combined. Here, the DNA bases, the peptide chains, and the sugar chains have roles not only for improving hydrophilicity but also for imparting intermolecular interactions such as a hydrogen bond.
For example, there has been developed a hydrogelator composed of a glycoside-amino acid derivative including a sugar structure moiety having a glycoside structure of N-acetylated monosaccharides or disaccharides (Patent Document 2) and a fine hollow fiber composed of a peptide lipid of General Formula “RCO(NHCH2CO)mOH” and a transition-metal and having self-assembling property (Patent Document 3).
There is also disclosed a formation of β-sheet fiber network from an amphiphilic peptide having a structure of <hydrophobic portion-cysteine residue (forming disulfide bonds at the time of network formation)-glycine residue (imparting flexibility)-phosphorylated serine residue-cell adhesive peptide> using the hydrophobic portion as a core (Non-patent Document 4).
There has been reported preparation of a glycolipid supermolecular hydrogel using a chemical library (Non-patent Document 5).
Amphiphilic dipeptide compounds composed of a hydrophobic portion and a dipeptide are also drawing attention as one of the “bottom-up type” functional materials capable of forming a self-assembly. For example, it is known that a dipeptide compound having a specific lipid part of “2-(naphthalen-2-yloxy)acetic acid” and “glycylglycine, glycylserine, or the like” can form a hydrogel. However, such compounds can form a gel from only an acidic aqueous solution or a hydrogel formed from each is acidic (Non-patent Document 6).
Furthermore, few of the low-molecular weight hydrogels that have been thus developed can form a gel not only from an aqueous solution but also from an organic solvent, and hydrogels capable of forming a gel from both of the solvents have a limited structure. Even hydrogels capable of forming a gel from both of the solvents can form a gel only from a combination of water or an aqueous solution having a limited pH and a specific organic solvent (Non-patent Documents 7 to 9). That is, there are no gelators that can form a gel from an aqueous solution in a wide pH range as well as have gelation properties with respect to an organic solvent including solvents practically used for cosmetics and the like.
In contrast, a lipid peptide compound composed of lauric acid or myristic acid that is a natural fatty acid and glycylglycine does not form a hydrogel but forms an organic nanotube including multilayered vesicles of a hollow having an inner diameter of about 50 to 90 nm to be precipitated (for example, Patent Document 3). On the other hand, it has been found that palmitoyl-Gly-Gly-His that is formed by adding histidine to the C-terminal of glycylglycine and bonding palmitic acid as a natural fatty acid to the N-terminal has gelation properties. Moreover, it has been reported that palmitoyl-Gly-Gly-Gly-His that is formed by bonding palmitic acid to a tetrapeptide in place of the tripeptide has high gelation properties at a lowest gelation concentration of only 0.03 wt % (Non-patent Document 10).
In this manner, it is supposed that when the hydrophilic portion has a longer peptide chain, the number of hydrogen bonds between lipid peptides increases, and thus a stably assembled lipid peptide can be obtained. However, it is unknown until now whether a lipid peptide compound is self-assembled to form a gel when the hydrophilic portion has a shorter peptide chain and thus the number of hydrogen bonds between lipid peptides decreases.
Furthermore, even by the palmitoyl-Gly-Gly-Gly-His, it has been reported until now that a gel can be formed only from a few mediums such as 1 N hydrochloric acid aqueous solution, neutral and basic aqueous solutions, and a mixed solution of ethanol and water, and there are no reports on gelation using various acids or inorganic salts and on gelation of organic solvents used for cosmetics and external medicines.